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         headline:Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells
         description:Krüppel-like factors (Klf) 4 and 5 are two closely related members of the Klf family, known to play key roles in cell cycle regulation, somatic cell reprogramming and pluripotency. Here we focus on the functional divergence between Klf4 and Klf5 in the inhibition of mouse embryonic stem (ES) cell differentiation. Using microarrays and chromatin immunoprecipitation coupled to ultra-high-throughput DNA sequencing, we show that Klf4 negatively regulates the expression of endodermal markers in the undifferentiated ES cells, including transcription factors involved in the commitment of pluripotent stem cells to endoderm differentiation. Knockdown of Klf4 enhances differentiation towards visceral and definitive endoderm. In contrast, Klf5 negatively regulates the expression of mesodermal markers, some of which control commitment to the mesoderm lineage, and knockdown of Klf5 specifically enhances differentiation towards mesoderm. We conclude that Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in murine ES cells. The Krüppel-like factors Klf4 and Klf5 have wide roles in cell biology including the regulation of pluripotency. In this study, Aksoy et al. demonstrate that Klf4 preferentially blocks the expression of endodermal markers in embryonic stem cells, whereas Klf5 negatively regulates mesodermal factors.
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      headline:Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells
      description:Krüppel-like factors (Klf) 4 and 5 are two closely related members of the Klf family, known to play key roles in cell cycle regulation, somatic cell reprogramming and pluripotency. Here we focus on the functional divergence between Klf4 and Klf5 in the inhibition of mouse embryonic stem (ES) cell differentiation. Using microarrays and chromatin immunoprecipitation coupled to ultra-high-throughput DNA sequencing, we show that Klf4 negatively regulates the expression of endodermal markers in the undifferentiated ES cells, including transcription factors involved in the commitment of pluripotent stem cells to endoderm differentiation. Knockdown of Klf4 enhances differentiation towards visceral and definitive endoderm. In contrast, Klf5 negatively regulates the expression of mesodermal markers, some of which control commitment to the mesoderm lineage, and knockdown of Klf5 specifically enhances differentiation towards mesoderm. We conclude that Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in murine ES cells. The Krüppel-like factors Klf4 and Klf5 have wide roles in cell biology including the regulation of pluripotency. In this study, Aksoy et al. demonstrate that Klf4 preferentially blocks the expression of endodermal markers in embryonic stem cells, whereas Klf5 negatively regulates mesodermal factors.
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         Cell signalling
         Embryogenesis
         Stem-cell differentiation
         Science
         Humanities and Social Sciences
         multidisciplinary
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               name:Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, Madrid, Spain
               type:PostalAddress
            type:Organization
      name:Norbert Hübner
      affiliation:
            name:Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10
            address:
               name:Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Lawrence W. Stanton
      affiliation:
            name:Genome Institute of Singapore, 60 Biopolis street
            address:
               name:Genome Institute of Singapore, 60 Biopolis street, Singapore, Singapore
               type:PostalAddress
            type:Organization
      name:Francisco X. Real
      affiliation:
            name:Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3
            address:
               name:Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, Madrid, Spain
               type:PostalAddress
            type:Organization
            name:Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
            address:
               name:Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
               type:PostalAddress
            type:Organization
      name:Pierre-Yves Bourillot
      affiliation:
            name:Inserm, U846, 18 Avenue Doyen Lepine
            address:
               name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
               type:PostalAddress
            type:Organization
            name:Stem Cell and Brain Research Institute
            address:
               name:Stem Cell and Brain Research Institute, Bron, France
               type:PostalAddress
            type:Organization
            name:Université de Lyon, Université Lyon 1
            address:
               name:Université de Lyon, Université Lyon 1, Lyon, France
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Pierre Savatier
      affiliation:
            name:Inserm, U846, 18 Avenue Doyen Lepine
            address:
               name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
               type:PostalAddress
            type:Organization
            name:Stem Cell and Brain Research Institute
            address:
               name:Stem Cell and Brain Research Institute, Bron, France
               type:PostalAddress
            type:Organization
            name:Université de Lyon, Université Lyon 1
            address:
               name:Université de Lyon, Université Lyon 1, Lyon, France
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
      name:Stem Cell and Brain Research Institute, Bron, France
      name:Université de Lyon, Université Lyon 1, Lyon, France
      name:Genome Institute of Singapore, 60 Biopolis street, Singapore, Singapore
      name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
      name:Stem Cell and Brain Research Institute, Bron, France
      name:Université de Lyon, Université Lyon 1, Lyon, France
      name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
      name:Stem Cell and Brain Research Institute, Bron, France
      name:Université de Lyon, Université Lyon 1, Lyon, France
      name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
      name:Stem Cell and Brain Research Institute, Bron, France
      name:Université de Lyon, Université Lyon 1, Lyon, France
      name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
      name:Stem Cell and Brain Research Institute, Bron, France
      name:Université de Lyon, Université Lyon 1, Lyon, France
      name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
      name:Stem Cell and Brain Research Institute, Bron, France
      name:Université de Lyon, Université Lyon 1, Lyon, France
      name:Genome Institute of Singapore, 60 Biopolis street, Singapore, Singapore
      name:Genome Institute of Singapore, 60 Biopolis street, Singapore, Singapore
      name:Genome Regulation Laboratory, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
      name:Genome Institute of Singapore, 60 Biopolis street, Singapore, Singapore
      name:Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, Berlin, Germany
      name:Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, Berlin, Germany
      name:Center for Genomic Regulation (CRG), C. Dr. Aiguader 88, Barcelona, Spain
      name:Universitat Pompeu Fabra (UPF), C. Dr. Aiguader 88, Barcelona, Spain
      name:Universitat Pompeu Fabra (UPF), C. Dr. Aiguader 88, Barcelona, Spain
      name:Present address: Stem Cell Center, Masonic Medical Research Laboratory, Utica, New York-13501, USA,
      name:Center of Physiology and Pathophysiology, Institute of Neurophysiology, Robert-Koch-Strasse. 39, Cologne, Germany
      name:Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin, Germany
      name:Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin, Germany
      name:Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, Madrid, Spain
      name:Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin, Germany
      name:Genome Institute of Singapore, 60 Biopolis street, Singapore, Singapore
      name:Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, Madrid, Spain
      name:Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
      name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
      name:Stem Cell and Brain Research Institute, Bron, France
      name:Université de Lyon, Université Lyon 1, Lyon, France
      name:Inserm, U846, 18 Avenue Doyen Lepine, Bron, France
      name:Stem Cell and Brain Research Institute, Bron, France
      name:Université de Lyon, Université Lyon 1, Lyon, France
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